1- Primary Immunodeficiencies unit, Leuven University hospital, Belgium
2- Unidade de Imunodeficiências Primárias, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
- ESID European Society for Immunodeficiencies, apresentação sob forma de poster
Background and aims: Hypomorphic homozygous mutations of LIG4, encoding DNA ligase IV, cause a wide spectrum of developmental and immune defects, from SCID presentations to a phenotype resembling other chromosomal instability syndromes. Most patients present growth failure, microcephaly, facial dysmorphism and mental retardation, diverse skin and bone manifestations and an immunodeficiency ranging from severe combined immunodeficiency to isolated humoral deficiency. In some cases isolated bone marrow failure and hematological malignancies have been reported.
Methods: Whole exome sequencing (WES) was performed in a 24-year-old man who was healthy until the age of 16 years-old, when he presented suppurative hidradenitis. Two years after, he was hospitalized for a pneumonia, which resolved uneventfully. At the age of 21 he had a complicated pneumonia caused by serotype B Haemophillus (isolated on blood cultures). At that time he was found to have absent IgG, IgA and IgM and no responses to recall antigens. He had no B cells but had normal T-cell subset. He is a tall, overweigth patient with no dysmorphic features,no bone abnormlities but presenting vitiligo. He has been on SCIg replacement and is on perfect condition since diagnosis.
Results: WES identified a homozygous mutation in LIG4 (p.R278H), already reported in the literature as pathogenic, resulting in radiosensitivity and in a subtle VDJ recombination defect.?
Conclusions: We report the first DNA Ligase IV deficienct patient with isolated late-onset agammaglobulinemia and vitiligo. Once again, an unbiased next generation sequencing approach is helpful to study patients with ill-identified features of immunodeficiency.
Palavras Chave: Agammaglobulinemia, DNA repair, Ligase IV